e., the alarming platelet count) nor the target, i.e., the platelet number posttransfusion before invasive procedures, are evidence-based. Laboratory methods that may help determine the trigger/target platelet count needed before invasive procedures are also lacking. Some years ago Lisman et al,[6] provided in vitro evidence that the adhesion of platelets from patients with cirrhosis to

the subendothelial matrix was normal despite the fact that these patients were thrombocytopenic. This is explained by the increased levels of the adhesive protein von Willebrand factor, which is a typical feature of patients with cirrhosis.[6] Recently, we showed in an in vitro study of platelet-rich plasma that the threshold platelet count needed to secure thrombin generation Belinostat correspondent to the lower limit of the normal reference range amounts to 56 × 109/L.[7] However, the methods employed in the Lisman et al.[6] and in our study,[7] although useful to shed light on the mechanisms of adhesiveness and thrombin generation mediated by platelets in cirrhosis, are not yet applicable to manage patients. Furthermore, in another study we showed that the prophylactic transfusion of selleck one single adult platelet unit (often used regardless of the pretransfusion platelet counts) is barely sufficient to increase platelet counts above 50 × 109/L and that both

thrombin generation and thromboelastometry (i.e., a global method that assesses Cobimetinib concentration the viscoelastic properties of clotting blood) were barely affected by this transfusion schedule.[8] Accordingly, if a greater platelet count is required, this requires multiple transfusions. Thrombopoietin receptor agonists that are able to increase platelet counts in chronic idiopathic thrombocytopenic purpura may present an alternative to multiple transfusions.[9] In a recent issue of the New England Journal of Medicine, Afdhal et al.[10] reported interesting results on a randomized/controlled clinical trial of one such oral agent (eltrombopag) for its ability to spare platelet transfusion in patients with cirrhosis undergoing an elective invasive procedure. The study was timely, as platelet transfusions have some limitations (short duration of efficacy,

risk of transfusion reactions, and development of antiplatelet antibodies). Patients with platelet counts equal or lower than 50 × 109/L were randomized to receive eltrombopag 75 mg once daily or placebo.[10] A platelet transfusion was avoided in 72% of the patients who received eltrombopag and in 19% of those who received placebo. No significant difference between the eltrombopag (17% of patients) and placebo (23% of patients) groups was observed in bleeding episodes of World Health Organization (WHO) grade 2 or higher.[10] However, thrombotic events of the portal venous system were observed in six patients who received eltrombopag, as compared with one who received placebo. Because of this, the investigators opted for an early termination of the study.

e., the alarming platelet count) nor the target, i.e., the platelet number posttransfusion before invasive procedures, are evidence-based. Laboratory methods that may help determine the trigger/target platelet count needed before invasive procedures are also lacking. Some years ago Lisman et al,[6] provided in vitro evidence that the adhesion of platelets from patients with cirrhosis to

the subendothelial matrix was normal despite the fact that these patients were thrombocytopenic. This is explained by the increased levels of the adhesive protein von Willebrand factor, which is a typical feature of patients with cirrhosis.[6] Recently, we showed in an in vitro study of platelet-rich plasma that the threshold platelet count needed to secure thrombin generation see more correspondent to the lower limit of the normal reference range amounts to 56 × 109/L.[7] However, the methods employed in the Lisman et al.[6] and in our study,[7] although useful to shed light on the mechanisms of adhesiveness and thrombin generation mediated by platelets in cirrhosis, are not yet applicable to manage patients. Furthermore, in another study we showed that the prophylactic transfusion of find more one single adult platelet unit (often used regardless of the pretransfusion platelet counts) is barely sufficient to increase platelet counts above 50 × 109/L and that both

thrombin generation and thromboelastometry (i.e., a global method that assesses Dipeptidyl peptidase the viscoelastic properties of clotting blood) were barely affected by this transfusion schedule.[8] Accordingly, if a greater platelet count is required, this requires multiple transfusions. Thrombopoietin receptor agonists that are able to increase platelet counts in chronic idiopathic thrombocytopenic purpura may present an alternative to multiple transfusions.[9] In a recent issue of the New England Journal of Medicine, Afdhal et al.[10] reported interesting results on a randomized/controlled clinical trial of one such oral agent (eltrombopag) for its ability to spare platelet transfusion in patients with cirrhosis undergoing an elective invasive procedure. The study was timely, as platelet transfusions have some limitations (short duration of efficacy,

risk of transfusion reactions, and development of antiplatelet antibodies). Patients with platelet counts equal or lower than 50 × 109/L were randomized to receive eltrombopag 75 mg once daily or placebo.[10] A platelet transfusion was avoided in 72% of the patients who received eltrombopag and in 19% of those who received placebo. No significant difference between the eltrombopag (17% of patients) and placebo (23% of patients) groups was observed in bleeding episodes of World Health Organization (WHO) grade 2 or higher.[10] However, thrombotic events of the portal venous system were observed in six patients who received eltrombopag, as compared with one who received placebo. Because of this, the investigators opted for an early termination of the study.

CD26 (DPPIV) recently was demonstrated directly involved in regulating IP-10 activity by NH2-terminal truncation. Lower sCD26 was associated with favorable treatment outcome of chronic hepatitis C. We hypothesized that vitamin D supplement, which was shown to improve CHC treatment response, might act upon restoring immune dysregulation in these patients through a pathway linked to the Th1/Th2 cytokines, IP-10 or CD26. METHODS: CHC patients with vitamin D deficiency were assigned to receive vitamin D supplement or placebo for 6 weeks. Baseline characteristics, serum 25-hydroxy vitamin D [25(OH)D] levels, Th1/Th2

cytokines, IP-10 and sCD26 levels were measured at baseline and at 6 weeks. MLN0128 RESULTS: A total of 80 CHC patients with vitamin MEK inhibitor D deficiency were randomized into two groups, 40 patients in each group. There were no significant differences in all baseline characteristics between two groups. At the end of study, only the mean 25(OH)D levels in vitamin D group were significantly increased from 21.07 to 48.44 ng/ml, (p<0.001). There were no significant differences in serum levels of all Th1/Th2 cytokines in both groups at the end of the study period. Importantly, while there were no significant changes of the IP-1 0 and sCD26 levels in placebo group, there were significant

decreased in serum levels of both chemokines in vitamin D group after 6-week of vitamin D supplement (p<0.05 and p<0.05, respectively) (Fig.1). CONCLUSIONS: Correction of vitamin D deficiency in CHC patients resulted in suppression of serum IP-1 0 and sCD26 levels without the effect on serum Th1/Th2 cytokines.These results, at least, identified an immuno-pathophysiologic

link between an important chemo-tactic chemokine with its regulating molecule (sCD26) and effects of vitamin D replacement therapy, and provided an explanation of why vitamin D deficiency might have an effect on CHC treatment responses. Disclosures: The following people have nothing to disclose: Kriangsak Charoensuk, Chintana Chirathaworn, Sirinporn Suksawatamnuay, Panarat Thaimai, Kessarin Thanapirom, Kittiyod Poovorawan, Pinit Kullavanijaya, Piyawat Komolmit Objective: Rho Persistent hepatitis C virus (HCV) infection causes not only liver disease but also extrahepatic effects, such as type 2 diabetes. Patients with chronic hepatitis C (CHC) complicated by type 2 diabetes show resistance to interferon (IFN) therapy. Selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance and plays an important role in the pathogen-esis of type 2 diabetes (Cell Metab. 201 0); however, its effects on IFN signaling have not been clarified. Methods: SeP gene expression was suppressed in Huh-7.

CD26 (DPPIV) recently was demonstrated directly involved in regulating IP-10 activity by NH2-terminal truncation. Lower sCD26 was associated with favorable treatment outcome of chronic hepatitis C. We hypothesized that vitamin D supplement, which was shown to improve CHC treatment response, might act upon restoring immune dysregulation in these patients through a pathway linked to the Th1/Th2 cytokines, IP-10 or CD26. METHODS: CHC patients with vitamin D deficiency were assigned to receive vitamin D supplement or placebo for 6 weeks. Baseline characteristics, serum 25-hydroxy vitamin D [25(OH)D] levels, Th1/Th2

cytokines, IP-10 and sCD26 levels were measured at baseline and at 6 weeks. SB203580 cost RESULTS: A total of 80 CHC patients with vitamin Metabolism inhibitor D deficiency were randomized into two groups, 40 patients in each group. There were no significant differences in all baseline characteristics between two groups. At the end of study, only the mean 25(OH)D levels in vitamin D group were significantly increased from 21.07 to 48.44 ng/ml, (p<0.001). There were no significant differences in serum levels of all Th1/Th2 cytokines in both groups at the end of the study period. Importantly, while there were no significant changes of the IP-1 0 and sCD26 levels in placebo group, there were significant

decreased in serum levels of both chemokines in vitamin D group after 6-week of vitamin D supplement (p<0.05 and p<0.05, respectively) (Fig.1). CONCLUSIONS: Correction of vitamin D deficiency in CHC patients resulted in suppression of serum IP-1 0 and sCD26 levels without the effect on serum Th1/Th2 cytokines.These results, at least, identified an immuno-pathophysiologic

link between an important chemo-tactic chemokine with its regulating molecule (sCD26) and effects of vitamin D replacement therapy, and provided an explanation of why vitamin D deficiency might have an effect on CHC treatment responses. Disclosures: The following people have nothing to disclose: Kriangsak Charoensuk, Chintana Chirathaworn, Sirinporn Suksawatamnuay, Panarat Thaimai, Kessarin Thanapirom, Kittiyod Poovorawan, Pinit Kullavanijaya, Piyawat Komolmit Objective: Methane monooxygenase Persistent hepatitis C virus (HCV) infection causes not only liver disease but also extrahepatic effects, such as type 2 diabetes. Patients with chronic hepatitis C (CHC) complicated by type 2 diabetes show resistance to interferon (IFN) therapy. Selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance and plays an important role in the pathogen-esis of type 2 diabetes (Cell Metab. 201 0); however, its effects on IFN signaling have not been clarified. Methods: SeP gene expression was suppressed in Huh-7.

Before the initial visit, caregivers consented to answer the questionnaire via telephone. Patients’ medical records were reviewed after haematological evaluation. VWF:Ag or VWF:RCo<30 IU dL−1 were labelled ‘definite type 1 click here VWD’ while 30–50 IU dL−1 were labelled ‘Low VWF’. PFA-100 screening followed by abnormal electron microscopy and/or platelet aggregation studies diagnosed a PFD. At least one haemorrhagic

symptom was present in 99 of the 104 children who completed the study (mean number of symptoms 2.87, mean Vicenza score 3.24). Eight met criteria for ‘definite type 1 VWD’, 23 for ‘low VWF’ and 13 for ‘PFD’. The sensitivity, specificity, and positive and negative predictive value (NPV) of the Vicenza score demonstrated poor diagnostic utility with the exception of high specificity in ruling out ‘definite type

1 VWD’. The NPV was comparably high with qualitative (>2 bleeding symptoms) and quantitative (Vicenza score ≥2) criteria. The Vicenza score has limited predictive value in paediatric tertiary care settings. While the NPV of excluding ‘definite type 1 VWD’ is high, simpler qualitative criteria is similarly predictive. “
“Most countries still do not achieve 1 IU of factor VIII/capita sufficient for survival. Selleckchem Venetoclax Although primary prophylaxis prevents synovitis, is not universally used. Chronic synovitis is treated with arthroscopy at expense of considerable amount of coagulation factors, and specialized surgeons. Radioactive synovectomy (RS) is a minimally invasive and cost effective alternative to arthroscopy, often considered first the option for persistent synovitis. Even without established causation with cancer, RS is avoided

by some, due to this concern. We aim contributing to the understanding of RS safety regarding malignancy, presenting a large number of treated patients, and a single case of cancer. Three centres in Brazil applied RS with 90Yttrium Citrate, 90Yttrium hydroxyapatite or 153Samarium hydroxyapatite selleck screening library in haemophilic joints and performed a survey addressing cancer in these patients. Four hundred and eighty eight patients (ages 3–51) received 1–3 RS (total 842) and follow-up was 6 months to 9 years. One patient aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated successfully with surgery and chemotherapy. Causality of cancer by RS is improbable in this case. Accordingly, latency here is far below minimum 5–10 years for radio-induction of solid tumours. Moreover, ES is not a typically radio-induced tumour, even at high doses. In agreement with others, though recognizing limitations, this study suggests RS is safe regarding cancer induction. Synovitis is a known burden for patients. The decision of making reasonable usage of RS should be outweighed with the risks of leaving synovitis untreated. “
“Summary.

By immunofluorescence, four KO livers showed less than 1% β-catenin-positive hepatocytes, whereas two KO livers had around 20%-30% spontaneous repopulation (Fig. 3C). Five additional KO livers showed less than 1% hepatocytes to be β-catenin-positive in the KO by IHC as well (data not shown). Thus, a majority of the KO livers did not show many β-catenin-positive hepatocytes at baseline, suggesting only a DDC injury-dependent spontaneous repopulation

with β-catenin-positive hepatocytes, which may have initially escaped albumin-cre driven β-catenin deletion. However, a very small subset of KO livers did show the presence of greater numbers click here of β-catenin-positive cells for unknown reasons, albeit nowhere to the extent observed after DDC exposure. Previously, we reported that β-catenin is strongly positive in bile duct epithelia in normal liver, whereas it is lacking in the KO despite the fact that conditional deletion of the floxed gene was brought about by the albumin-cre, perhaps due to embryonal expression of albumin in a common progenitor of hepatocytes and cholangiocytes.9 Next we address if β-catenin-positive biliary epithelial cells, which have also been shown to be the precursors of oval cells, may be the source of β-catenin-positive hepatocytes in the KO liver.11 A comprehensive analysis selleck compound showed that

none of the bile ducts in the KO livers were β-catenin-positive at baseline and 7 or 30 days of DDC exposure, as indicated by a lack of colocalization of β-catenin and A6, which is known to be a marker of biliary ductular epithelia and oval cells in the liver (Fig. 3B).1, 12 Most bile ducts continued to be β-catenin-negative in the KO livers after 80 days of DDC exposure, whereas in WT livers all bile ducts (atypical and atypical) were strongly β-catenin-positive (Fig. 3D). At this

stage only an occasional bile duct was lined by β-catenin-positive epithelia, whereas at 150 days a few additional ducts Adenosine triphosphate were β-catenin-positive (Fig. 3D). Thus, appearance of β-catenin-positive hepatocytes precedes the appearance of β-catenin-positive bile ducts in the KO liver at baseline as well as after chronic DDC injury and hence cannot be the source of repopulation. To examine whether the increase in the number of β-catenin-positive hepatocytes correlates with a decrease in expression of the transgene, we performed real-time PCR analysis for Cre-recombinase at 30, 80, and 150 days after DDC feeding. Real-time PCR analysis was performed for Cre-recombinase in three separate mouse livers using three different reference genes. The analysis showed that there was no significant difference in mRNA expression of Cre-recombinase between untreated age- and sex-matched KO mouse livers and the 30 days DDC-fed KO livers (data not shown).

Thus, a substantial involvement of a high-latitude refugium in the post-glacial colonization of Europe by bank voles is inferred. Likely as the consequence of the high-latitude survival, the Carpathian clade lacks evidence of the severe demographic bottleneck during the Last Glacial Maximum that is observed in the Eastern clade.

The contact zone between the expanding populations of the Carpathian and Eastern clades coincides with subdivisions in other species and may represent a new post-glacial suture zone. “
“Environmental factors can directly influence phenotype such that a tight correlation between morphological and environmental variation is expected. However, morphological response to environmental variation may also reflect constraints imposed PD98059 by interactions between adjacent structures such as the gills and the trophic apparatus in fishes. Such complex interactions help to explain why an organism’s phenotype may appear mismatched with its environment. This study quantified relationships between morphological traits related to feeding and respiration Natural Product Library purchase and the physico-chemical environment in a widespread cichlid fish Astatoreochromis alluaudi, from six sites in Uganda. This species is known to be plastic in jaw morphology with enlarged jaw morphs specialized for mollusk eating, and reduced jaw morphs for insect eating. However, recent studies suggest a mismatch between the trophic morphology and feeding ecology in field populations

of this species that could reflect interactions with the branchial apparatus; the development of large gills in low-oxygen habitats may constrain or affect pharyngeal jaw size. MANCOVA results for morphometric data showed Carbachol a strong population effect for both gill and jaw traits. We found a significant negative correlation between composite morphological variables (principle components) relating to the size and shape of gill apparatus and pharyngeal jaw size across all populations. Furthermore, gill traits generated from principle component

analysis were positively correlated with water conductivity, which was highly correlated with dissolved oxygen (DO) across the six sites. These results suggest that a particular morphological trait (pharyngeal jaw size) can be indirectly altered by the physico-chemical environment (conductivity and DO) due to correlated effects on a functionally unrelated morphology (gill size). These results have important implications for understanding species distribution patterns because trade-offs between suites of traits may constrain an individual’s ability to exploit an otherwise suitable habitat or resource. “
“There is still no uncontroversial agreement on the geographical variation, subspecies taxonomy and phylogenetic relationships between major populations of the lion Panthera leo. This study examines the patterns of geographical variation and phylogenetics of lions based on an extensive morphometric analysis on 255 wild lion skulls.

Administration of anabolic hormone together with energy substrates seems to be the most effective means to efficiently improve protein kinetics. “
“Wedemeyer H, Yurdaydìn C, Dalekos GN, Erhardt A, Çakaloğlu Y, Değertekin H, et al.; for HIDIT Study Group. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med 2011;364:322-331. (Reprinted with permission.) BACKGROUND: Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) results in the most severe form of viral hepatitis. There is no currently approved

treatment. We check details investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone, and adefovir dipivoxil alone. METHODS: We conducted a randomized

trial in which 31 patients with HDV infection received treatment with 180 μg of peginterferon alfa-2a weekly plus 10 mg of adefovir daily, 29 received 180 μg of peginterferon alfa-2a weekly plus placebo, and 30 received 10 mg of adefovir alone weekly for 48 weeks. Follow-up was conducted for an additional 24 weeks. Efficacy end points included clearance of HDV RNA, normalization of alanine aminotransferase levels, and a decline in levels of hepatitis B surface antigen (HBsAg). RESULTS: The primary end point—normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48—was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving Imatinib cost peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative Amylase in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P=0.006 for the comparison of the first and third groups; P=0.004 for the comparison of the second and third). The efficacy of peginterferon

alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log10 IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P<0.001 for the comparison of the first and third groups and P=0.01 for the comparison of the first and second). CONCLUSIONS: Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection. Since its discovery in 1977 by Rizzetto et al., hepatitis delta virus (HDV) has been known as a special and incomplete virus with an extraordinarily small RNA genome (1.7 kb) encoding two hepatitis D antigens (HDAgs): a small, 24-kDa HDAg and a bigger, 27-kDa HDAg.

This new entity raises the question of a novel autonomic dysfunction in short-lasting unilateral neuralgiform headaches with cranial autonomic symptoms

or an unexpected presentation of migraine. “
“Recent research has uncovered associations between migraine and experiencing traumatic events, the latter of which in some cases eventuates in the development of posttraumatic stress disorder (PTSD). However, existing studies have not attempted to explore the relative associations with migraine between experiencing trauma and suffering from PTSD. The aim of this cross-sectional study was to assess the predictive utility of trauma exposure vs PTSD in predicting migraine status and headache frequency, severity, and disability. One thousand fifty-one young adults (mean age = 18.9 years [SD = 1.4]; 63.1% female; 20.6% selleck chemical non-Caucasian) without secondary causes of headache provided data from measures of headache symptomatology and disability, trauma and PTSD symptomatology, and depression and anxiety. Three hundred met diagnostic criteria for migraine and were compared on trauma exposure and PTSD prevalence with 751 participants without migraine. Seven hundred

twenty-eight participants (69.3%) reported experiencing at least 1 traumatic event consistent with Criterion A for PTSD, of whom 184 also met diagnostic criteria for PTSD. Migraineurs were almost Daporinad cell line twice as likely as controls to meet criteria for PTSD (25.7% vs 14.2%, P < .0001) and reported a higher number of traumatic event

types that happened to them personally (3.0 vs 2.4, P < .0001). However, experiencing a Criterion A event only was not a significant predictor of migraine either alone (odds ratio [OR] = 1.17, P = nonsignificant) or after adjustment for covariates. By comparison, the OR of migraine for those with a PTSD diagnosis (vs no Criterion A event) was 2.30 (P < .0001), which remained significant after controlling for relevant covariates (OR = 1.75, P = .009). When using continuous variables of trauma and PTSD symptomatology, PTSD was again most strongly associated with migraine. Numerous sensitivity analyses confirmed these findings. PTSD symptomatology, but not the number of traumas, was modestly but significantly associated with headache frequency, severity, and disability in univariate analyses. Consistently across analyses, PTSD next was a robust predictor of migraine, whereas trauma exposure alone was not. These data support the notion that it is not exposure to trauma itself that is principally associated with migraine, but rather the development and severity of PTSD symptoms resulting from such exposure. “
“(Headache 2010;50:231-241) Objectives.— A population-based cross-sectional study was conducted to estimate the prevalence of migraine, episodic tension-type headaches (ETTH), and chronic daily headaches (CDH), as well as the presence of symptoms of temporomandibular disorders (TMD) in the adult population. Background.

To determine

adhesion ability, the total number of germlings incubated for 24 h in the circles was first counted under the microscope and then washed by dipping in distilled water 100 times vertically to remove the detached infection structures. Subsequently, the remaining germlings in the corresponding circle were counted again. Adhesion ability was assessed by the percentage of the number of the germlings that remained in comparison with the number before washing. All experiments were repeated three times. Droplets of M. oryzae Br48 spore suspension and enzymes (20 μL each) were inoculated on wheat leaves and placed in the dark in a moistened box at 25 °C. Six hours after incubation, the inoculated seedlings were gently washed with running water. The seedlings were incubated for a further 3 days and symptoms were observed. Disease symptoms

Ponatinib Enzalutamide were evaluated by the severity of the inoculated spot as follows: 5 – typical spore suspension lesion (control), 4 – 70% of control, 3 – 50% of control, 2 – 20% of control, 1 – 10% of control, 0 – no symptoms. Experiments were repeated three times. For SEM, droplets of a 20-μL spore suspension were inoculated on wheat leaves and from 6 to 24 hpi the droplets were replaced by each enzyme solution (20 μL) and the seedlings incubated in an environment-controlled room with fluorescent lighting at 25 °C up to 25 hpi. The inoculated seedlings were then gently washed under running water. The washed leaves were cut to approximately 1 × 1 cm and fixed with a freeze-drying method (Nemoto et al., 1992). The specimens were placed in a freeze-drying copper container (Nissin EM) that was designed for fungi and the container submerged in liquid nitrogen until its surface was completely frozen. The container with specimen was placed in a freeze-drying machine (Nissin EM) to evaporate the ice crystals of container completely. The specimens were retrieved from

the container and fixed with Org 27569 osmium tetroxide vapor for 2 h. Subsequently, the specimens were coated with platinum by an ion-sputtering device (E-1010; Hitachi), and three pieces of leaf were observed in every treatment (200 germlings or vestiges of the presence of the germlings were evaluated for each leaf) with SEM (S-3500N; Hitachi). The spores were incubated on plastic substrates for 0, 1, or 6 h, and each sample then subjected to treatment with each enzyme. In the enzyme treatments at 0 hpi, most of the spores germinated on the substrate (data not shown). However, appressorium formation was significantly inhibited (<50%) by the treatment with β-1,3-glucanase, α-mannosidase, β-mannosidase, lipase, α-chymotrypsin, pepsin, pronase E, trypsin, and collagenases (crude, type I type 4, type V, and type N-2), and was moderately inhibited (65–75%) by the treatment with protease or gelatinase B (Fig. 1).